Trial record 5 of 143 for:    Enzalutamide

Enzalutamide in Combination With Carboplatin and Paclitaxel in Endometrial Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2016 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02684227
First received: February 12, 2016
Last updated: April 7, 2016
Last verified: April 2016
  Purpose

This clinical research study has two parts: a safety lead-in and Phase 2.

The goal of the safety lead-in is to find the highest tolerable dose of enzalutamide in combination with carboplatin and paclitaxel that can be given to patients with recurrent or advanced endometrial cancer.

The goal of Phase 2 of this study is to learn if the study drug combination can help to control recurrent or advanced endometrial cancer.

The safety of the drug combination will be studied in both parts of the study.


Condition Intervention Phase
Endometrial Cancer
Drug: Enzalutamide
Drug: Carboplatin
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study With a Limited Safety Lead-In of Enzalutamide in Combination With Carboplatin and Paclitaxel in Advanced Stage or Recurrent Endometrioid Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Enzalutamide, in Combination with Paclitaxel and Carboplatin in Previously Untreated Participants with Advanced and Recurrent Endometrioid Endometrial Cancer [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    MTD determined if 2 or fewer participants out of 6 experience dose limiting toxicities (DLTs), then the regimen deemed safe for administration in the phase II study.


Secondary Outcome Measures:
  • Objective Tumor Response of Enzalutamide, in Combination with Paclitaxel and Carboplatin in Previously Untreated Participants with Advanced and Recurrent Endometrioid Endometrial Cancer [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Objective tumor response is (complete response (CR) + partial response (PR)). Response evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)22.


Estimated Enrollment: 69
Study Start Date: June 2016
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide + Carboplatin and Paclitaxel

Safety Lead-in Phase (Part A) - Participants receive Carboplatin and Paclitaxel by vein on Day 1 of Cycles 1 - 9. Participants also take Enzalutamide by mouth every day.

Phase II (Part B): Participants take Enzalutamide by mouth every day by itself during the first cycle (called Cycle 0). Participants then Receive Paclitaxel and Carboplatin by vein on Day 1 of Cycles 1-9. Participants continue taking Enzalutamide every day during this time.

Study cycle is 21 days.

Drug: Enzalutamide

Safety Lead-in Phase (Part A) Starting Dose: 160 mg by mouth daily of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Enzalutamide taken every day by itself during the first cycle (called Cycle 0).

Other Names:
  • MDV3100
  • XTANDI
Drug: Carboplatin

Safety Lead-in Phase (Part A) Starting Dose: Area under curve (AUC)= 5 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Carboplatin given by vein on Day 1 of Cycles 1 - 9.

Other Name: Paraplatin
Drug: Paclitaxel

Safety Lead-in Phase (Part A) Starting Dose: 175 mg/m2 by vein on Day 1 of Cycles 1 - 9 of a 21 day cycle.

Phase II (Part B) Starting Dose: Maximum tolerated dose (MTD) from Safety Lead-in Phase (Part A). Paclitaxel given by vein on Day 1 of Cycles 1 - 9.

Other Name: Taxol

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of advanced stage (stage III or IV) or recurrent endometrioid endometrial cancer.
  2. Measurable disease (at least one measurable lesion) IS required. A measurable lesion is one that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be > 10 mm when measured by CT scan, MRI, or caliper measurement by clinical exam; or > 20 mm when measured by Chest X-Ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
  3. Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
  4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status </= 1.
  5. Life expectancy of greater than 3 months in the opinion of the principal investigator.
  6. Recovery from effects of recent surgery, radiotherapy, or chemotherapy.
  7. Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
  8. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration.
  9. Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration.
  10. PRIOR THERAPY: Patients should have had NO prior chemotherapy agents for advanced or recurrent endometrial cancer. Prior chemotherapy administration in conjunction with primary radiation therapy as a radiosensitizer would NOT exclude a patient from participation in this trial.
  11. Patients must have adequate: (1) Bone marrow function: Absolute neutrophil count (ANC) >/= 1,500/mcl, equivalent to Common Terminology Criteria (CTCAE v4.03) grade 1; Platelets >/= 100,000/mcl; (2) Renal function: calculated creatinine clearance (Cockcroft-Gault formula) > 50 ml/min OR 24-hour urine creatinine clearance > 50 ml/min; (3) Hepatic function: Bilirubin </= 1.5 x ULN (CTCAE v4.03 grade 1; in patients with known Gilbert Syndrome, a total bilirubin </=3.0 x ULN, with direct bilirubin </= 1.5 x ULN). AST and alkaline phosphatase </= 2.5 x ULN (CTCAE v4.03 grade 1; AST and ALT </= 3 x ULN (or </= 5.0 x ULN if hepatic metastases are present); (4) Neurologic function: Neuropathy (sensory and motor) </= CTCAE v4.03 grade 1; [Continued in Criterion 12]
  12. [Continued from Criterion 11] (5) PT such that international normalized ratio (INR) is </= 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT </= 1.5 times the institutional upper limit of normal. Patients receiving low molecular weight heparin for the prevention or treatment of venous thromboembolic disease are eligible if considered clinically stable on their regimen.
  13. Patients must have signed an approved informed consent.
  14. Age >/=18 years. Because no dosing or adverse event data are currently available on the use of enzalutamide in combination with carboplatin and paclitaxel in patients <18 years of age, children are excluded from this study.
  15. The effects of enzalutamide on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial may be teratogenic, women of child-bearing potential and their partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential (intact uterus) should have a negative serum pregnancy test. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Patients must be able to swallow whole tablets.
  16. With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE v4 Grade 1 at the time of starting study treatment.
  17. Patients must be willing to undergo pre- and post-treatment biopsies.

Exclusion Criteria:

  1. Patients who have isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery.
  2. Patients with the following histologies of endometrial cancer are not eligible for enrollment: papillary serous adenocarcinoma, clear cell carcinoma, adenosquamous carcinoma, mucinous adenocarcinoma, carcinosarcoma, sarcoma.
  3. Prior Therapy: Prior Chemotherapy: Patients who have had a prior chemotherapy regimen for advanced or metastatic disease are excluded. Prior Radiation Therapy: Patients may have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy, alone or with chemotherapy as a radiation sensitizer. All radiation therapy must be completed at least 4 weeks prior to the first date of study therapy. The prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided at registration.
  4. Patients who have previously received enzalutamide. Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
  5. Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (CTCAE v4.03 grade 2 or greater, excluding alopecia) due to agents administered more than 4 weeks earlier.
  6. Patients may not receive any other anti-neoplastic or investigational agents within 3 weeks of study enrollment. Patients may not be receiving any other investigational agents during treatment on protocol.
  7. Patients may not receive strong CYP2C8 inhibitors, CYP2C8 inducers, or CYP3A4 inducers. In addition, patients should not receive drugs that are metabolized by CYP3A4 or CYP2C9.
  8. Patients who are pregnant or nursing. The effects of enzalutamide on the developing human fetus are unknown. For this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  9. Patient had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery.
  10. Patients may not have a history of other malignancies except for basal cell or squamous cell skin cancer, in situ cervical cancer, unless they have been disease-free for at least five years.
  11. Patients with predisposing factors for seizure including history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastasis, and brain arteriovenous malformation.
  12. Patient with history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to enzalutamide, carboplatin, or paclitaxel.
  13. Patients may not have symptomatic, uncontrolled spinal cord compression and/or brain metastases. A scan to confirm absence of brain metastasis is not required. Patients can receive a stable dose of corticosteroids before/ during study if these were started at least 28 days prior to entry.
  14. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease], uncontrolled chronic renal diseases [glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension (blood pressure >/= 160/90), active bleeding diatheses or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
  15. As judged by the Investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02684227

Contacts
Contact: Shannon Westin, MD 713-794-4314

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Astellas Pharma Inc
Medivation, Inc.
Investigators
Principal Investigator: Shannon Westin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02684227     History of Changes
Other Study ID Numbers: 2015-0723 
Study First Received: February 12, 2016
Last Updated: April 7, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Endometrial cancer
Advanced Stage Endometrioid Endometrial Cancer
Recurrent Endometrioid Endometrial Cancer
Enzalutamide
MDV3100
XTANDI
Carboplatin
Paclitaxel
Taxol

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Albumin-Bound Paclitaxel
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators

ClinicalTrials.gov processed this record on May 26, 2016